Activation of 5-HT7 receptor in rat glomerulosa cells is associated with an increase in adenylyl cyclase activity and calcium influx through T-type calcium channels

被引：61

作者：

Lenglet, S ^{[1
]}

Louiset, E ^{[1
]}

Delarue, C ^{[1
]}

Vaudry, H ^{[1
]}

Contesse, V ^{[1
]}

机构：

[1] Univ Rouen, CNRS, INSERM U413,European Inst Peptide Res, Lab Cellular & Mol Neuroendocrinol,Unite Affiliee, F-76821 Mont St Aignan, France

来源：

ENDOCRINOLOGY | 2002年 / 143卷 / 05期

关键词：

D O I：

10.1210/en.143.5.1748

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Serotonin (5-HT) stimulates aldosterone secretion from the rat adrenal gland through 5-HT7 receptors. The aim of the present study was to investigate the transduction mechanisms associated with activation of 5-HT7 receptors in rat glomerulosa cells. The stimulatory effect of 5-HT on aldosterone secretion and cAMP formation was significantly reduced by the 5-HT7 receptor antagonist LY 215840. Pretreatment of cells with the adenylyl cyclase inhibitor SQ 22536 or the PKA inhibitor H-89 markedly attenuated the effect of 5-HT on aldosterone secretion. Conversely, type 2 and 4 phosphodiesterase inhibitors potentiated the 5-HT-induced stimulation of aldosterone secretion. Administration of 5-HT in the vicinity of cultured glomerulosa cells induced a slowly developing and robust increase in cytosolic calcium concentration ([Ca2+](i)). The effect of 5-HT on [Ca2+](i) was suppressed by mibefradil, a T-type calcium channel blocker. Patch-clamp studies confirmed that 5-HT activated a T-type calcium current. Mibefradil also induced a dose-dependent inhibition of 5-HT-induced aldosterone secretion. The sequence of events associated with activation of 5-HT7 receptors was investigated. The PKA inhibitor H-89 markedly attenuated both the [Ca2+](i) response and the activation of T-type calcium current induced by 5-HT. In contrast, reduction of the calcium concentration in the incubation medium did not affect 5-HT-induced cAMP formation. Preincubation of glomerulosa cells with cholera toxin abolished the stimulatory effect of 5-HT on aldosterone secretion, but pertussis toxin had no effect. Taken together, these data demonstrate that, in rat glomerulosa cells, activation of native 5-HT7 receptors stimulates cAMP formation through a G(salpha) protein, which in turn provokes calcium influx through T-type calcium channels. Both the adenylyl cyclase/PKA pathway and the calcium influx are involved in 5-HT-induced aldosterone secretion.

引用

页码：1748 / 1760

页数：13

共 55 条

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